Activation of the ras oncogene has been implicated as the causative agent in as many as 30% of all human tumors. Yet in spite of extensive work on the ras gene, including the identification of at least seven different ras genes and an increasing number of ras-like genes, almost nothing is known about the function of the ras proteins in higher eukaryotes. A recently characterized protein, termed ARF, is a component of the adenylate cyclase system and shares several features with ras, including size, location, and ability to bind GTP. Characterization of the binding and hydrolysis of guanine nucleoties by ras and ARF will be undertaken. A systematic search will then be conducted to identify factor(s) which increase either the exchange or hydrolysis of guanine nucleotides by these regulatory proteins. These studies should locate cellular targets for these proteins and may identify the physiological role of these proteins in cellular metabolism or proliferation.